1 research outputs found
Pharmacokinetics, Metabolism, and Partial Biodistribution of “Pincer Therapeutic” Nitazoxanide in Mice following Pulmonary Delivery of Inhalable Particles
Nitazoxanide (NTZ) induces autophagy
in mammalian cells and also
has mycobactericidal activity, displaying a two-pronged therapeutic
effect, on the host as well as the pathogen. The pharmacokinetics
and biodistribution of inhaled NTZ were investigated. Particles containing
NTZ in a matrix of PLGA were prepared by spray drying. HPLC and LC–MS/MS
methods were developed and validated. Particles were administered
as inhalations to mice. Drug concentrations in plasma and tissues
were estimated at different time points. Drug loading (∼36%),
entrapment efficiency (>90%), and the conversion of NTZ into metabolites
in plasma and lung homogenates were assessed satisfactorily by HPLC.
NTZ pharmacokinetics and biodistribution following intravenous administration
or inhalation were established by LC–MS. NTZ converted into
tizoxanide (99% in 30 min) and other metabolites. Pulmonary delivery
of NTZ entrapped in particles increased the half-life of the drug
by factors of 3, 12, and 200 in the plasma, lung tissue, and alveolar
macrophages, respectively. Targeted delivery and prolonged lung retention
along with dose sparing of the kidneys was observed upon pulmonary
delivery as compared to intravenous administration